Targeted versus conventional therapy in R/R Ph-like ALL

Patients with Philadelphia (Ph) chromosome-like B-cell acute lymphoblastic leukemia (B-ALL) have a similar gene expression profile to those with Ph-positive ALL; however, they lack a BCR::ABL1 translocation.¹ Treatment with conventional chemotherapies can result in poor outcomes due to  CRLF2 overexpression in patients with Ph-like ALL; therefore, it is important to evaluate the potential of novel and targeted therapies in these patients.

The ALL Hub has previously reported on treatment strategies for Ph-like ALL. Here, we summarize a recently published article by Desikan et al.¹ evaluating the outcomes of adult patients with relapsed/refractory CRLF2-rearranged B-ALL, published in American Journal of Hematology.¹

Study design¹

This retrospective analysis including patients with relapsed/refractory CRLF2-rearranged Ph-like ALL treated at the MD Anderson Cancer Center, Houston, US, between 2001 and 2021. Patients entered the study when they received their first therapy. CRLF2 expression, prior treatments, cytogenetics, and Janus kinase 2 (JAK2) mutational status were assessed for all patients. The study endpoints were relapse-free survival (RFS), calculated from response to salvage therapy to subsequent relapse or death, and overall survival (OS), calculated from study entry to death.

Results¹

Overall, 69 patients were included in the analysis, of which 41 patients had a CRLF2 overexpression and 26 patients having an accompanying CRLF2 fluorescence in situ hybridization performed; all 26 of these patients had a CRLF2 rearrangement. Patients were split into two cohorts based on their first salvage therapy at the institution with or without chemotherapy (targeted therapy cohort), or conventional chemotherapy (conventional therapy cohort). Targeted therapies included inotuzumab ozogamicin and/or blinatumomab and/or CAR T-cell therapy. Patient characteristics are shown in Table 1. The majority of patients were male and Hispanic.

Efficacy

Median follow-up was 46 months. The rate of complete remission/complete remission with incomplete count recovery is shown in Figure 1, with overall survival (OS) shown in Figure 2.

Table 1. Baseline patient characteristics*

Figure 1. Response rates*

CR/CRi, complete remission/complete remission with incomplete count recovery.
*Adapted from Desikan, et al.¹

Figure 2. Overall survivial*

*Adapted from Desikan, et al.¹ 

When OS was analyzed based on JAK2 mutation status, patients with JAK2 mutations had a shorter median OS compared to patients with wild-type mutations (5.8 vs 10.5 months, respectively).

Conclusion¹

This study demonstrated that targeted therapies can improve outcomes in patients with Ph-like ALL, compared with patients treated with conventional chemotherapy. Although OS was higher in patients treated with target therapy, this difference was not statistically significant, potentially due to the small cohort sizes. Several limitations were noted, including patients entering the study at different time points during salvage therapy and patients receiving various prior therapies; this potentially restricted the evaluation of each therapy type and associated outcomes. Further, larger studies are warranted to evaluate the addition targeted therapies into Ph-like ALL treatment,  providing insight into the optimal treatment regimen for these patients.